The analysis of a substance to determine its composition may be necessary for many applications, including toxicology, forensics and environmental testing, as well as food and drug research. Often, samples to be analyzed are analyzed for the presence of numerous different analytes of interest. Such samples may, for example, be in the form of bodily fluids taken from test subjects, which fluids often include both drug metabolites of interest, as well as irrelevant endogenous ions from the test subject. Correctly determining the presence or absence of a large number of analytes of interest from complex substances can be difficult and time-consuming.
Mass spectrometers are often used for producing a mass spectrum of a sample to find its composition. This is normally achieved by ionizing the sample and separating ions of differing masses and recording their relative abundance by measuring intensities of ion flux. For example, with time-of-flight mass spectrometers, ions are pulsed to travel a predetermined flight path. The ions are then subsequently recorded by a detector. The amount of time that the ions take to reach the detector, the “time-of-flight”, may be used to calculate the ion's mass to charge ratio, m/z.
Additional information (in addition to an ion's precursor mass) can then be obtained by fragmenting the ion via CID (collision induced dissociation) in a collision cell (or other mean) to generate an MSMS spectrum. In most instruments with MSMS capabilities, the process of generating a mass spectrum, selecting a precursor ion and generating an MSMS (mass spectrum/mass spectrum) spectrum can be performed in an automated mode. This mode of acquisition is frequently referred to as Information Dependant Acquisition (IDA) or Data Dependant Experiment (DDE).
Chromatographic equipment such as a liquid chromatograph may be used to elute or release ions from a sample into the mass spectrometer over a period of time. Multiple reaction monitoring (MRM) or other distributed-analysis and recursive techniques may be used to analyze the ions received by the mass spectrometer.
Previous MRM techniques involve repeated cycles of scans by the mass spectrometer for predetermined analytes of interest. A “duty cycle” would involve a list of analytes to be “cycled through” and scanned for by the mass spectrometer. During MRM analysis, the mass spectrometer would divide its scans equally amongst the analytes of interest in the duty cycle. As a result, such duty cycles have a practical upper limit in the number of analytes which may be scanned for. Once the number of analytes grows too large (for example, some mass spectrometers require duty cycles to have no more than 50 analytes of interest in order to maintain acceptable data quality), the amount of scan time available for each analyte of interest is insufficient to provide accurate data.
The applicants have accordingly recognized a need for systems and methods for analyzing and identifying ions from samples.